This study investigated the association between ABO blood group and cancer risk in a Greek adult population. The study included 459 cancer patients and 918 non-cancer controls matched for age and gender. Multivariate analysis found that blood groups A and B were associated with significantly higher overall cancer risk compared to blood groups O and AB. Specifically, blood group A was associated with increased risk of gastric, colorectal, pancreatic, and lung cancer, while blood group B was associated with increased risk of esophageal cancer. The study provides evidence that ABO blood group is a risk factor for certain cancer types in Greek adults.

1. Journal of Clinical Research in Dentistry • Vol 3 • Issue 1 • 2020 13
INTRODUCTION
C
ancer is the second leading cause of death worldwide
and responsible for 9.6 million deaths in 2018. In
Europe, cancer causes the second highest number
of deaths after cardiovascular disease. Its development is a
result of interactions between genetics and environmental
factors.
Genetic factors include advanced age, male gender, cancer
family history, and genetic susceptibility. Especially, genetic
mutations are responsible for 5–10% of all cancer cases.[1]
Environmental etiological and risk factors include cigarette
smoking, and obesity, previous diseases such as infections
with hepatitis B or C (HBV/HCV), chronic obstructive
pulmonary disease, and radiation.
However, the mentioned etiological or risk factor scan
explain only a part of cancer incidence as its clear etiology
still remains unknown.[2,3]
Hereditary types of cancer show,
in general, a low prevalence, however, inherited biomarkers
such as ABO blood group have been associated with the
risk of various diseases and types of cancer according to the
previous and current researches.[3]
ORIGINAL ARTICLE
Association between ABO Blood Group and Various
Types of Cancer: A Case–Control Study in Greek
Adults
Nikolaos Andreas Chrysanthakopoulos
Oncologist (MSc Oncol), PhD in Oncol (cand), Department of Pathological Anatomy, Medical School, University
of Athens, 401 General Military Hospital of Athens, Athens, Greece
ABSTRACT
Introduction:The association betweenABO blood group and cancer has been identified in many epidemiological researches.
The aim of the current research was to investigate the association between ABO blood group and the risk of several types
of cancer in a Greek adult population. Materials and Methods: A total of 459 individuals who suffered from various
types of cancer and 918 non-cancer individuals were enrolled. Blood group data obtained from registration on identity
patient’s card. The associations between ABO blood group and cancer estimated using a multivariate logistic regression
analysis model, whereas a multinomial model was carried out to estimate adjusted odds ratios for each type of cancer
separately. Results: The risk of overall cancer in blood groups A and B individuals was significantly higher than that in O
and AB groups, (P = 0.001, OR = 1.96, 95%CI = 1.33–2.87, and P ≤ 0.0001, OR = 2.04 95% CI=1.43–2.90, respectively).
Compared to blood type O, blood type A was significantly associated with an increased risk of gastric (P = 0.002, OR = 2.55,
95% CI = 0.55–4.30), colorectal (P = 0.046, OR = 2.06, 95%CI = 0.82–2.58), pancreatic (P = 0.034, OR = 2.23, 95%
CI = 1.02–2.83), and lung cancer (LC) (P = 0.022, OR = 2.78, 95% CI = 1.63–5.49), whereas blood type B was significantly
associated with an increased risk of esophagus cancer (P = 0.051, OR = 1.26, 95% CI = 0.83–1.50), after adjusting for age,
gender, educational and socio-economic status, smoking, and family history of cancer. Conclusion: The overall cancer risk
in blood groups A and B individuals was significantly higher compared to blood type O and AB, whereas blood type A was
significantly associated with an increased risk of gastric, colorectal, pancreatic, and LC.
Key words: ABO blood group, Adults, Cancer, Risk factors
Address for correspondence:
Dr. Nikolaos Andreas Chrysanthakopoulos, 35, Zaimi Street, PC 26 223, Patra, Greece.
https://doi.org/10.33309/2639-8281.030105 www.asclepiusopen.com
© 2020 The Author(s). This open access article is distributed under a Creative Commons Attribution (CC-BY) 4.0 license.

2. Chrysanthakopoulos: Association between ABO Blood Group and Cancer
14 Journal of Clinical Research in Dentistry • Vol 3 • Issue 1 • 2020
The ABO blood groups system discovered decades ago,[4]
is the most immunogenic of all the blood group antigens,
its antigens are biomarkers expressed in various types of
cells including erythrocytes, mucosa, lung epithelial, and
gastrointestinal cells.[5,6]
The ABO gene is an autosomal
gene that is located on chromosome 9 at q34.1–q34.2 region
and encodes for a specific glycosyltransferase enzyme that
adds a glucose residue to a carbohydrate structure, the H
antigen, that is present in the membrane of erythrocytes
and other types of endothelial and epithelial cells as already
mentioned.[7]
Distribution of the four different blood groups
varies among countries in different geographical, ethnic,
and socioeconomic groups.[8]
In general, blood group shows
the highest prevalence, while blood Group AB shows
the lowest. Although the elaborate physiologic function
of the ABO blood group antigens remains unknown, no
disease results from the lack of ABO blood group antigens
expression.[7]
An association between ABO blood group and various
diseases was proposed 50 years ago.[9]
In recent years, several
reports haves shown that ABO blood group was associated
with many diseases and pathological conditions and various
types of cancer,[10,11]
although the explanation for that
relationship is still not understood. Most recent reports based
on the finding that such an association was initially suggested
through the observation that gastric cancer (GC) patients were
more likely to have blood type A than control individuals,[12]
documented a relative link between susceptibility to cancer
and ABO blood group or found a relationship between ABO
blood group and risk of certain malignancies.
In herited human ABO blood group, antigens were associated
withvarioustypesofmalignanciesincludingpancreatic,[10,13-20]
renal cell,[21]
skin,[11]
ovarian,[22,23]
esophageal,[16,24-26]
hepatocellular,[27,28]
colorectal,[16,29]
oral cavity,[30-33]
larynx,[34]
bladder,[35]
breast,[36]
gastric,[12,16,17,37-40]
prostate,[41]
and lung
cancer (LC),[16,42-45]
but the associations, in general, were
inconsistent. For instance, an association between ABO
blood group and nasopharyngeal cancer (NPC) remains
controversial as a research by Seow et al.[46]
demonstrated
the absence of such an association, whereas Turkoz et al.[47]
found that ABO blood group was associated with NPC
susceptibility. Similarly, previous reports investigated the
possible association between ABO blood group antigens and
risk of LC and proposed a possible association; however, the
data on the role of ABO blood group factor in LC are limited
and inconsistent.[42,44,45]
Most previous studies were based on self-reporting of blood
type which is prone to recall and information biases. In
addition, the relative small sample sizes of most previous
studies have limited the opportunity to comprehensively
estimate the link between ABO blood group and cancer risks,
particularly for rare types of cancers.
Similar retro- or prospective studies of the association
between ABO blood group and cancer risk have not been
carried out in Greece.
The aim of the present retrospective case–control study was
to investigate the possible association between ABO blood
groups and risk of cancer overall and separately, in several
organs in an adult population sample in Greece.
MATERIALS AND METHODS
Study design and study sample
A total of 459 individuals, 200 males and 259 females, who
were suffering from various types of cancer and 918 non-
cancer individuals, 473 males and 445 females, aged 45–74
years who were selected from two private medical practices
enrolled in the study.
The current study was a retrospective case–control study. The
case group included patients with several types of cancer and
its diagnosis was confirmed according to histopathological
examination of their medical files. The attempt was to choose
the controls in such a way they can be the representatives of
the population from which the cases were drawn. Thus, cases
and controls were selected from the same city population
in an effort to avoid or eliminate possible selection biases.
In addition, the selection of controls was based on cases’
environment, such as friends and colleagues. According to
that method, eligible control individuals were selected from
those, who were subjected to routine health examinations
at the mentioned practices, between 2015 and 2018. Both
groups, cases and controls, were matched 2–1 with cancer
patients for age (± 5 year), and gender in an effort to control
potential confounders.
Cancer rates were estimated according to cancer mortality
rates in 2012 as no data were available which concerned
cancer incidence in Greece.[48]
Participants included in the study completed a baseline
questionnaire about common risk factors for cancer. Thus,
they completed a self-administered questionnaire which
concerned information on their medical history, smoking
status, socio-economic and educational level, and cancer
family history. When at least one first-degree family member
was diagnosed with cancer, the family history was considered
positive for cancer. The cases who had distant metastases in
any-one of the organs examined or had a medical history
of other malignancies were excluded and included patients
with newly diagnosed cancer who were out-patients of
the mentioned medical practices in an effort to eliminate
potential effects by known and unknown confounders.
ABO blood group was confirmed by the medical files of the
participants.

3. Chrysanthakopoulos: Association between ABO Blood Group and Cancer
Journal of Clinical Research in Dentistry • Vol 3 • Issue 1 • 2020 15
Statistical analysis
The associations between ABO blood group and risk of
overall cancer were assessed using univariate and multivariate
logistic regression analysis. Adjusted odds ratios (AOR’s)
and 95% confidence interval (CI) were recorded as well.
The independent variables were included in Wald method
to assess gradually the variables which showed significant
associations with the dependent one.
Finally, a multinomial model was carried out to estimate
AOR’s between ABO blood group and the risk of each type
of cancer separately, after adjusting for potential confounders,
such as age, gender, smoking status, educational and socio-
economic level, and family history of cancer. In this analysis,
blood type O was used as a reference group.
Statistical analysis was performed using the statistical
package of SPSS ver.19.0. P 5% (P 0.05) was considered
to be statistically significant.
RESULTS
The distribution of blood groups of controls was similar to
the general Greek population.
Cases and controls showed a mean age of 64.5 years (± 3.7).
The distribution of cancer patients and controls with ABO
group and the univariate analysis are shown in Table 1.
According to univariate analysis age, educational level,
smoking, cancer family history, and ABO blood group were
found to be significantly associated with overall cancer risk.
The same table shows that the frequency of overall cancer
risk was significantly higher in blood Group A individuals
(P = 0.043), whereas blood Group AB individuals had lower
overall cancer risk as compared to controls.
Table 2 presents the distribution of each cancer type according
to the variables examined.
Table 3 presents the results after performing of the
multivariate regression model. Step1 – Enter method showed
that smoking (P = 0.000, OR = 1.77, 95%CI = 1.39–2.26),
cancer family history (P = 0.000, OR = 1.84, 95% CI = 1.45–
2.33), A (P = 0.001, OR = 1.94, 95%CI = 1.32–2.85), and B
(P = 0.000, OR = 2.01, 95% CI = 1.41–2.86) blood groups
were significantly associated with overall cancer risk.
Step 4 – Wald method showed that the mentioned indices,
smoking (P = 0.000, OR = 1.72, 95% CI = 1.36–2.17),
cancer family history (P = 0.000, OR = 1.85, 95% CI = 1.47–
2.34), A (P = 0.001, OR = 1.96, 95% CI = 1.33–2.87), and
B (P = 0.000, OR = 2.04, 95% CI = 1.4–2.90), including male
gender (P = 0.046, OR = 1.27, 95% CI = 1.01–1.60), were
significantly associated with overall cancer risk. The same
table also shows AOR’s and 95% CI.
Table 4 shows the AOR’s and 95%CI of ABO blood group
categories to each type of cancer.
Table 1: Univariate analysis of cases and controls regarding each independent variable examined
Variables Cases (No) (%) Controls (No) (%) P-value Odds ratio 95% confidence interval
Gender: Males 259 (56.4) 473 (51.5)
Females 200 (43.6) 445 (48.5) 0.086 0.82 0.66-1.03
Age (years): 45–49 104 (22.7) 277 (30.2)
50–59 164 (35.7) 286 (31.2) 0.010* ___ ___
60–69 157 (34.2) 271 (29.5)
70+ 34 (7.4) 84 (9.2)
Socio-economic level: Low 287 (62.5) 539 (58.7)
High 172 (37.5) 379 (41.3) 0.173 1.17 0.93–1.48
Educational level: Low 242 (52.7) 828 (65.2)
High 217 (47.3) 442 (34.8) 0.000* 0.60 0.48–0.74
Smoking: No 148 (32.2) 480 (52.3)
Yes 311 (67.8) 438 (47.7) 0.000* 0.43 0.34–0.55
Cancer family history: No 204 (44.4) 476 (51.9)
Yes 255 (55.6) 442 (48.1) 0.010* 0.74 0.59–0.913
ABO blood group: O 108 (23.5) 244 (26.6)
A 225 (49.0) 391 (42.6) 0.043* ____ ________
B 80 (17.4) 153 (16.7)
AB 46 (10.0) 130 (14.2)
*P-value: Statistically significant

4. Chrysanthakopoulos: Association between ABO Blood Group and Cancer
16 Journal of Clinical Research in Dentistry • Vol 3 • Issue 1 • 2020
Gastric, colorectal, pancreatic, and LC were significantly
associated with blood Group A, whereas esophageal
cancer was significantly associated with blood Group B
after performance of multinomial regression model and
after adjusting for age, gender, educational level and socio
economic status, smoking, and family history of cancer.
DISCUSSION
The association between ABO blood type and many diseases
has been investigated for more than 50 years; however,
findings to date have little practical value as prevention
indices.
The results showed that GC risk was higher among individuals
with blood type A than those with blood type O. Many
similar studies have found such an association, however,
no clear evidence has been suggested,[16,17,38,39]
whereas it
has also been recorded that individuals with blood Group O
demonstrated a decreased risk of GC,[12,37-39]
and in a previous
overview was observed an inverse association for blood
Group O compared to non-O groups.[16]
The heterogeneity
among studies reviewed could be a possible explanation for
those findings.[16]
Only one study[10]
failed to confirm the
relationship between ABO blood groups and GC.
An increased risk of ESOC for individuals with blood
Group B was also found, whereas the significance level was
marginal (P = 0.051), and the sample of ESOC individuals was
extremely low. Similar findings were observed in the previous
studies.[16,24-26]
In another report was recorded that ESOC risk for
blood Group O was significantly lower than non-O groups.[16]
Table 2: Distribution of each type of cancer according to independent variables
Variables OC and
NPC
OEC GC CRC HCC PC LC
n (%) n (%) n (%) n (%) n (%) n (%) n (%)
Gender
Males 7 (70.0) 5 (71.4) 29 (60.4) 38 (45.2) 28 (53.8) 28 (58.3) 124 (59.0)
Females 3 (30.0) 2 (28.6) 19 (39.6) 46 (54.8) 24 (46.2) 20 (41.7) 86 (41.0)
Age (years)
45–49 2 (20.0) 1 (14.3) 8 (16.7) 28 (33.3) 12 (23.1) 8 (16.7) 45 (21.4)
50–59 3 (30.0) 1 (14.3) 25 (52.1) 38 (45.2) 15 (28.8) 25 (52.1) 57 (27.1)
60–69 3 (30.0) 3 (42.9) 11 (22.9) 15 (17.9) 17 (32.7) 10 (20.8) 98 (46.7)
70+ 2 (20.0) 2 (28.5) 4 (8.3) 3 (3.56) 8 (15.4) 5 (10.4) 10 (4.8)
Socio-economic level
Low 6 (60.0) 5 (71.4) 32 (66.7) 37 (44.0) 27 (51.9) 12 (25.0) 168 (80.0)
High 4 (40.0) 2 (28.6) 16 (33.3) 47 (56.0) 25 (48.1) 36 (75.0) 42 (20.0)
Educational level
Low 7 (70.0) 4 (57.2) 30 (62.5) 32 (38.1) 31 (59.6) 17 (35.4) 121 (57.6)
High 3 (30.0) 3 (42.8) 18 (37.5) 52 (61.9) 21 (40.4) 31 (64.6) 89 (42.4)
Smoking
No 2 (20.0) 1 (14.2) 14 (29.2) 18 (21.4) 17 (32.7) 13 (27.1) 83 (39.5)
Yes 8 (80.0) 6 (85.7) 34 (70.8) 66 (78.6) 35 (67.3) 35 (72.9) 127 (60.5)
Cancer family history
No 3 (30.0) 2 (28.6) 18 (37.5) 35 (41.7) 23 (44.2) 20 (41.7) 103 (49.0)
Yes 7 (70.0) 5 (71.4) 30 (62.5) 49 (58.3) 29 (55.8) 28 (58.3) 107 (51.0)
ABO blood group
O 1 (10.0) 1 (14.2) 9 (18.8) 21 (25.0) 10 (19.2) 13 (27.1) 53 (25.2)
A 3 (30.0) 2 (28.6) 21 (43.8) 38 (45.2) 24 (46.1) 18 (37.5) 119 (56.7)
B 4 (40.0) 2 (28.6) 10 (20.8) 13 (15.4) 12 (23.1) 12 (35.0) 27 (12.8)
AB 2 (20.0) 2 (28.6) 8 (16.6) 12 (14.4) 6 (11.6) 5 (10.4) 11 (5.3)
Total 10 7 48 84 52 48 210
OC and NPC: Oral and nasopharyngeal cancer, OEC: Esophageal cancer, GC: Gastric cancer, CRC: Colorectal cancer, HCC:
Hepatocellular cancer, PC: Pancreatic cancer, LC: Lung cancer

5. Chrysanthakopoulos: Association between ABO Blood Group and Cancer
Journal of Clinical Research in Dentistry • Vol 3 • Issue 1 • 2020 17
The current study showed that individuals with blood Group
A had as significantly increased risk of colorectal cancer
(CRC) compared to those with non-A blood group, findings
that were in agreement with those from a previous report.[29]
A decreased risk of CRC for individuals with blood Group
O was recorded in a systematic review; however, a high
heterogeneity was found among the studies examined.[16]
On
the contrary, similar previous reports found no association.[49]
Individuals with blood group a had an increased risk of LC
in the current report. In a similar multicenter retrospective
study recorded that non-O blood type was associated with
an increased risk of LC, and blood Group O was associated
with a 14% risk reduction of LC,[42]
whereas a significant
excess risk was found among individuals with blood Group
A in another study.[43]
In contrary to previous, similar reports
recorded no association between ABO blood groups and
risk of LC.[44,45]
A protective effect of LC for blood Group B
compared to non-B groups was shown in a review, but was
not statistically significant, whereas statistically significant
heterogeneity was observed among the studies reviewed.[16]
The possible association between ABO blood group and
pancreatic cancer (PC) risk has been investigating for decades,
however, that association has not been consistently recorded.
A significant association was observed in the current study
between blood type A and the risk of PC, finding that was
confirmed by previous and recent studies.[10,14,18,19]
A meta-
analysis showed that only one study recorded an inverse
association for blood Group A compared to non-A groups,
but was not statistically significant, where as a median
heterogeneity was present.[16]
In contrary to those findings,
similar studies recorded increased rates of blood Group B
among PC patients.[15,17]
In addition, the previous reports suggested that compared
with blood Group O individuals, those with non-O blood
types (A, AB, or B) were more likely to develop PC, or were
associated with an elevated risk of PC.[17]
It has also been
demonstrated that blood Group O individuals had a lower
risk of PC,[13]
compared with blood Groups A and AB.[13]
Only one study revealed that blood Group AB was protective
against PC risk.[20]
Table 3: Presentation of correlation between independent variables and overall cancer according to Enter (1a
step) and Wald (4a step) method of multivariate logistic regression analysis model
Variables in the equation
Variables 95% C.I. for EXP (B)
B S.E. Wald df Sig Exp(B) Lower Upper
Step 1a
Gender 0.226 0.119 3.563 1 0.059 1.253 0.991 1.584
Age 0.010 0.062 0.025 1 0.875 1.010 0.894 1.141
Smok.stat 0.570 0.124 20.974 1 0.000* 1.768 1.386 2.257
Educ.level 0.225 0.132 2.918 1 0.088 1.252 0.967 1.621
Socioec.lev -0.138 0.133 1.083 1 0.298 0.871 0.671 1.130
Family hist 0.608 0.122 24.934 1 0.000* 1.837 1.447 2.332
O group 23.651 1 0.000
A group 0.660 0.196 11.302 3 0.001* 1.936 1.317 2.845
B group 0.696 0.181 14.782 1 0.000* 2.007 1.407 2.862
AB group 0.150 0.203 0.544 1 0.461 1.162 0.780 1.729
Constant 1.921 0.214 80.960 1 0.000 0.146
Step 4a
Gender 0.238 0.119 3.999 1 0.046* 1.269 1.005 1.602
Smok.stat 0.540 0.119 20.626 1 0.000* 1.716 1.359 2.166
Family hist 0.617 0.120 26.605 1 0.000* 1.853 1.466 2.343
O group 23.956 3 0.000
A group 0.672 0.196 11.772 1 0.001* 1.957 1.334 2.873
B group 0.711 0.181 15.491 1 0.000* 2.035 1.429 2.900
AB group 0.173 0.201 0.739 1 0.390 1.189 0.801 1.764
Constant 1.869 0.191 95.730 1 0.000 0.154
The reference category is: O blood group/ Smok.status: Smoking status, educ.level: Educational level, socioec.lev: Socioeconomic level,
Family hist: Family history. *P-value: statistically significant

6. Chrysanthakopoulos: Association between ABO Blood Group and Cancer
Journal of Clinical Research in Dentistry • Vol 3 • Issue 1 • 2020
No association was observed between ABO blood group and
the risk of hepatocellular cancer HCC. However, previous
studies observed associations between the ABO blood group
and liver diseases including HCC.[28]
Recent reports found
higher risk for HCC in the presence of A antigen,[27,43,50]
while it also found that males with blood type A or B had
a significantly higher HCC risk compared with males with
blood Type O which was independent of the known HCC risk
factors.[27]
On the basis of the current study, no association was recorded
between the ABO blood group and the risk of ONPC, findings
that were in agreement with those of recent genome wide
association studies on NPC.[51]
In the contrary, previous
studies have shown that blood Group B individuals were at
a greater risk to develop OC.[31,32]
Similarly, cancer of the
buccal mucosa blood Group B showed the highest frequency;
however, it was not statistically significant.[52]
Blood Group A
individuals showed a higher risk of developing OC[33]
or were
more susceptible to the development of OC,[47]
whereas blood
Group O had a protective effect.[47]
In a systematic review and
meta-analysis was found that NPC risk for blood GroupAwas
significantly higher than non-A groups and for blood group
O the risk was significantly lower than non-O groups,
without evidence of heterogeneity across studies.[16]
Table 4: Presentation of correlation between ABO blood group and each type cancer according to multinomial
logistic regression analysis model
Cancer general 95% C.I. for EXP(B)
Interval for Exp(B)
Sig. Exp(B) Lower
bound
Upper
bound
Oral and nasopharyngeal Ca
A group 0.098 0.936 0.516 1.387
B group 0.118 0.673 0.347 1.148
AB group 0.214 0.549 0.313 1.133
Esophageal cancer
A group 0.068 1.297 0.485 1.194
B group 0.051 1.225 0.825 1.502
AB group 0.302 0.872 0.443 1.108
Gastric cancer
A group 0.002 2.552 0.546 4.297
B group 0.061 1.907 0.774 2.698
AB group 0.536 0.857 0.239 1.284
Colorectal cancer
A group 0.046 2.059 0.815 2.579
B group 0.078 1.308 0.623 1.748
AB group 0.119 1.113 0.445 1.274
Hepatocellular cancer
A group 0.103 0.613 0.212 1.176
B group 0.066 1.112 0.483 1.62
AB group 0.087 0.949 0.490 1.203
Pancreatic cancer
A group 0.034 2.297 1.023 2.826
B group 0.077 1.049 0.575 1.424
AB group 0.337 0.541 0.285 1.177
Lung cancer
A group 0.022 2.783 1.627 5.486
B group 0.178 1.147 0.694 1.298
AB group 0.251 0.912 0.542 1.031

7. Chrysanthakopoulos: Association between ABO Blood Group and Cancer
Journal of Clinical Research in Dentistry • Vol 3 • Issue 1 • 2020 19
Another similar research recorded that blood Types A or
AB was associated with an increased risk of NPC.[53]
Those
differences could be attributed to diversity in sample
size, study design, and races of participants, whereas the
association between ABO blood groups and the cancer risk
may vary among different geographic locations and races
or ethnicities.[11]
The biological mechanism by which genetic variants in
ABO gene locus influence the risk of GC still remains
unknown. The antigens ABO/ABH are crucial intercellular
adhesion and membrane signaling mediators, are involved
in the malignant cells progression and dissemination[54]
and, are also recognized by the host immune system and
may affect immunosurveillance for malignant cells.[54]
Another explanation is the differences found among ABO
alleles in atrophic gastritis prevalence and Helicobacter
pylori infection, as both conditions are risk factors for GC
development.[40]
A potential explanation for the increased
incidence of GC in blood Group A individuals could be
the fact that those individuals were more susceptible to
pernicious anemia, compared with non-A blood group
ones,[55]
as individuals who suffer from pernicious anemia
are more prone to GC.[56]
A possible explanation for the
association between ABO blood types and risk of CRC could
be the alterations on theABH blood group antigens which can
change the cell-cell and cell-extracellular matrix interactions,
abnormalities that can lead to tumor development, and the
alteration of ABO/Lewis antigen that have been found to be
related to malignant transformation in some tumors.[57]
One
hypothesis proposes that the difference in ABO antigens in
gastric mucins affects the properties of H. Pylori binding,
and explains the difference in PC risk among ABO blood
types,[20]
whereas was found that only the A1 allele was
associated with significantly higher risk for pancreatic ductal
adenocarcinoma after comparison ABO allele frequencies
in PC patients and blood donors.[58]
Chronic pancreatitis is a
predisposing factor for pancreatic tumorigenesis,[59]
and the
ABO blood antigens may affect the systemic inflammatory
reaction.
Tumor necrosis factor-α (TNF-α) is a pro-inflammatory
cytokine which regulates pancreatic ductal cell apoptosis,[59]
whereas plasma levels of soluble inter-cellular adhesion
molecule (sICAM-1) are associated with the risk of diabetes
mellitus development,[60]
which increases the susceptibility
for PC. It is possible that ABO antigens may alter the
systemic inflammatory conditions and influence the risk of
PC development. It has also been shown the deletion and
the novel expression of A, B, and Hantigens on the PC cells
surface compared with surrounding normal ductal cells,[6]
suggesting that alterations in glycosyltransferase specificity
may occur during pancreatic tumorigenesis. Alterations
in the host inflammatory state due to ABO blood antigens
may provide a further mechanism to explain such an
association.[61]
ABO blood group is associated with various
serum biomarkers such as the inflammatory associated
cytokines TNF-α, epidermal growth factor (EGF), sICAM-
1, P-selectin, E-selectin,[62,63]
and EGF receptor which
are involved in HCC development,[64]
whereas its gene
polymorphisms have been suggested to be associated with
HCC risk.[65]
ABO antigens act as receptors or ligands for
bacteria and immunologically enzymes that are involved
in malignant progression and dissemination.[54]
Thus, the
abnormalABO blood antigens expression in liver cells tissue
might be associated with HC carcinogenesis. In healthy liver
cells, the ABO blood antigens A, B, and H, are not expressed
on their surfaces, however, increased ABH expression or neo
expression has been found in HCC cells.[66]
The non-O blood
group is an independent risk factor for the progression of
liver fibrosis in HCV infection,[67]
whereas individuals with
blood Group A show more liver dysfunction and earlier
appearance of liver cirrhosis compared to those with blood
Group A.[27]
Those observations suggest an association
between ABO blood groups and liver inflammation and
fibrosis progression inpatients with HCV which can lead
to HC carcinogenesis. Previous investigations indicated
that ABO antigens mediate microbial infections, including
H. pylori[14]
and Norwalkvirus.[68]
Thus, it is possible that
ABO status may also interact with EBV and influence NP
carcinogenesis. However, the lack of information on EBV
infections sets limits the current study, which may display a
bias in the analysis.
The current case–control study has certain limitations
as does not have the reliability of the prospective ones,
whereas selection, recall, random, referral biases, and the
effect of known and unknown con-founders are likely higher
and could lead to biased secondary associations. Possible
confounding factors which are related with increased risk
of various types cancer were not included. The results for
overall cancer may be conducted by the cancer sites with
more studies included, as the number of studies on different
cancer sites included in the current study varied largely.
Another limitation relates to the selection of controls, which
may attitude a challenge for ABO phenotype and other
features with anABO distribution which varies by geography
and ethnicity. Although the current study had a relatively
large sample size in general, the number of individuals in
some subgroups was small. In addition, the data analyses
based on cancer mortality as data which concerned the
cancer incidence in Greece were not available. Some
strengths of the current study were that it was a matched
case–control study, and used randomly selected population-
based controls. Potential limitations which concern each
type of cancer are also important. HCC could be attributed
to chronic hepatitis B/C; however, the data are insufficient
for our statistical analysis. The number of ONP and ESO
cancer patients in the current study was insufficient for
analysis. A potential source of bias was the medical status of

8. Chrysanthakopoulos: Association between ABO Blood Group and Cancer
20 Journal of Clinical Research in Dentistry • Vol 3 • Issue 1 • 2020
the controls. Lack of consideration of chronic pancreatitis
as a potential cause of PC in the analysis could also be a
limitation in the present study. In addition, the current study
did not examine the possible susceptibility to PC in diabetic
cases. Finally, some of the known risk factors of cancer
were examined and not specific as drinking consumption,
previous infection by EBV, exposure to atmosphere
pollutants, nutrition habits, etc.
CONCLUSION
The current study showed that the overall cancer risk in
blood Group A and B individuals was significantly higher
compared to blood type O and AB, whereas blood type
A was significantly associated with an increased risk of
gastric, colorectal, pancreatic, and LC, and blood type B was
significantly associated with an increased risk of esophagus
cancer.
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How to cite this article: Chrysanthakopoulos NA.
Association between ABO Blood Group and Various
Types of Cancer: A Case-Control Study in Greek Adults. J
Clin Res Dent 2020;3(1):13-22.